[Hypertensive acting 5-(beta-aminoethyl)aminoisoxazoles: synthesis and screening of derivatives with with partially rigid C-5 side chains and omega-position heterocyclics].
Isoxazoles with a 1,2-diaminoethane side chain at C-5 are synthesized by nucleophilic substitution of 5-chloro derivatives. Using piperazine, imidazolidine and 1,2-diaminocyclohexane, resp., isoxazoles with partially rigid chains at C-5 are formed. The same procedure succeeds in the synthesis of isoxazoles having a heterocycle at the omega-position of the side chain. The hypertensive activity of all new compounds is shown for the pithed and the anaesthetized rat, resp. According to structure activity relationships the hypertensive activity of compounds 7 and 8, resp., is mainly determined by the heterocycle at the omega-position (piperazine greater than piperidine approximately pyrrolidine greater than morpholine). Derivatives 2-5 with partially rigid 5-(beta-aminoethyl)amino side chains show less hypertensive activity than the corresponding compounds without restrictions.
Dannhardt
G
G
Institut für Pharmazeutische Chemie, Johann Wolfgang Goethe-Universität, Frankfurt am Main.
Dominiak
P
P
Laufer
S
S
D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D003655:Decerebrate State; D003959:Diamines / Q000138:chemical synthesis* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D003959:Diamines; D007555:Isoxazoles
Hypertensiv wirksame 5-(beta-Aminoethyl)aminoisoxazole: Synthese und Prüfung von Derivaten mit teilrigidisierter C-5-Seitenkette bzw. omega-ständigem Heterocyclus.